Our goal is to understand the interactions responsible for the calcium-dependent, high-affinity interaction of calmodulin with target enzymes. Our general approach is to examine structural and dynamic consequences of the interaction of calmodulin with peptides corresponding to the calmodulin binding domains of regulated enzymes. These studies should augment, unify and clarify a wide body of information regarding the underlying principles of calcium-dependent regulation of enzymes by calmodulin. Specifically, we will determine the structures of the bound peptides by using isotopically enriched peptides in combination with heteronuclear spectroscopy and characterize the stability of their secondary structure by hydrogen exchange and NMR relaxation methods; refine our current model for the structure of the complex of calmodulin and peptide corresponding to the smooth muscle myosin light chain kinase calmodulin-binding domain (smMLCKp); undertake the resonance assignment and structural characterization of the high affinity complexes of calmodulin with the binding domain of neuromodulin; undertake the resonance assignment and structural characterization of the high affinity complexes of calmodulin with the binding domains of phosphorylase b.